One in 40 Ashkenazi Jews susceptible to cancer

GILLIAN KLAWANSKY

Mutation means there is permanent alteration in the DNA sequence that makes up a gene.

Yet, only Ashkenazi Jews with a history of cancer in their families are advised to be tested for the gene. “There has to be a personal or family history,” says Johannesburg-based genetic counsellor, Kara Stoler, who also works at the Malka Ella Fertility Fund. “We want to see how many generations the cancer goes back in your family, at what age someone had cancer, and what cancer they had.”

“Family history combined with certain backgrounds increases the chance of a positive test,” says Dr Carol-Ann Benn, a South African expert on breast-cancer.

Both these factors applied to Kerri Segal, who tested positive for the BRCA gene in 2016. She decided to wait until she had children before getting tested. “My mom passed away 23 years ago from ovarian cancer when I was 16. My sister and I always said we’d get tested for the BRCA gene once we’d had our families because you don’t want to have a hysterectomy before you’re ready.”

Yet in April 2016, Segal’s sister, Tarryn Goldberg, then 38, was diagnosed with aggressive breast cancer, and had a double mastectomy. “Her oncologist suggested we both do genetic testing immediately because the blood changes during chemo,” recalls Segal, who was 36 at the time.

Segal says that she and Goldberg were informed about the gene’s prevalence amongst Ashkenazi Jews, especially those with a strong family history. “My bobba [grandmother]had a melanoma,” says Segal, “and my mother had ovarian cancer which later spread – she passed away at the age of 50. My mom was one of four girls, and one of her sisters had breast cancer and tested positive for BRCA1. The other two sisters were negative.”

“Tarryn and I had our blood tests at Lancet, and we were both positive. Before the test, our genetic counsellor discussed our options, and asked if we were prepared for the results and willing to do the risk-reducing operations. We could have embarked on intensive [cancer] screening, but the best way to alleviate the dark cloud, for us, was to do the operations.”

Both sisters ultimately had double mastectomies and oophorectomies – the removal of the ovaries, uterus, and fallopian tubes. “I’ve dealt with a lot in my life, and thank G-d, I’m very good at putting things in a box,” says Segal. “While I was going through it, I was like a soldier, I was very focused. But afterwards, I experienced post-traumatic stress.”

Segal says she still worries about the possibility of her daughters carrying the gene. “That was my biggest stress initially. But I’m told there are continuous advancements in breast-cancer prevention. We’ll test them only in their 20s, but it’s definitely a worry.” Goldberg is now cancer-free, and she and Segal both ran the 10km Jerusalem Marathon in 2018. Together, they raised more than R160 000 for DL Link, a non-profit centre focused on cancer patients and their families.

Dr Benn says BRCA testing isn’t as simple as going to a laboratory. One should be properly informed before being tested for the gene, she says. That’s why counselling by a genetic expert is essential. “People must understand what testing means and why, and they must know their family history.

“Genetic counselling is important because you need to sit with someone who explains exactly what your risks and your screening or preventative options are once you receive a positive result,” says Stoler. Because not everyone has BRCA1 or 2, Stoler does a full “hereditary cancer panel” when testing. “We don’t want to miss something, especially if there’s a strong family history.”

Most Ashkenazi genetic conditions, like Tay-Sachs and cystic fibrosis, are recessive, which means that both parents have to be carriers, says Stoler. Yet, BRCA is a dominant condition, which means only one parent must be the carrier to potentially pass it on to their offspring.

Why are Ashkenazi Jews predisposed to certain genetic mutations? “A group of people who are usually historically from one isolated geographic area develops a genetic mutation,” says Dr Benn. “This is then seen more frequently in that group.” In other words, a mutation appears in the DNA of one or more of the individuals within a distinct community of people. This mutation can then be passed down to future generations within this group that consists of individuals with a similar genetic makeup.

“Every population group has something different,” says Stoler.

For example, Central African people are at increased risk of sickle cell disease, and Afrikaans people are also at risk of BRCA mutations and familial hypercholesterolaemia.”

A BRCA gene mutation doesn’t automatically mean you will get cancer, but it does increase your risk of getting it. “With BRCA, we talk about a 60% to 80% lifetime chance of developing breast cancer,” says Dr Benn.

Only 2% of the women in the general population are at risk of ovarian cancer. Yet those with a BRCA mutation have up to a 60% lifetime risk, which increases as women enter their 40s. “Inherited BRCA gene mutations are responsible for about 5% to 10% of breast cancers, and about 15% of ovarian cancers,” says Stoler.

“But diseases, genes, and people don’t follow textbook guidelines,” cautions Dr Benn. Personal and lifestyle factors as well as pure luck also play a role in determining whether breast cancer will occur, and how it will present itself.

It’s also important to note that 65% of women diagnosed with breast cancer have no risk factors, whereas 20% have a family history of breast and other cancer, but are BRCA negative.

BRCA gene testing is simple and non-invasive. It involves either a blood or saliva test. When testing is covered by medical aid, blood tests are processed locally. Otherwise a saliva test is done in South Africa, and sent overseas for processing at a cost of about $250 (around R3 700). Those under 18 are not tested, and people are advised to wait until their 20s to test.

If a gene mutation is found, the options include risk-reducing surgery or enhanced cancer screening. Surgery can involve either a bilateral mastectomy and/or an oophorectomy. Surgery can be time dependent, and women need to consider things like their fertility or desire to breastfeed, says Stoler.

“Whereas one can ‘cut off breasts’ and ‘take out ovaries’, the same can’t be said for your skin or pancreas,” says Dr Benn. “Less than 20% of patients elect to do risk-reducing surgery. It isn’t cosmetic surgery, and has potential complications. It should always be discussed in detail, with a clear understanding of problems attached to any surgery.”

“In terms of screening, regular radiology and clinical screening is important. This includes ultrasounds twice yearly, mammography yearly from 35, and yearly MRI scans,” says Dr Benn. Monthly self-breast examinations are also vital.

With continuous advancements in fertility treatment, a future without inherited genetic conditions is possible. “Because couples don’t want to pass on any known genetic conditions to their children, undergoing an IVF protocol and screening the embryos – known as preimplantation genetic diagnosis – has become more common,” says Stoler. Here, only embryos without genetic mutations are implanted in the womb.